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With an ongoing transition towards the use of Light Emitting Diodes, more knowledge is needed on which light settings optimise sustainability parameters in pig production. We studied the effects of four light intensities on social, environmental and economic sustainability indicators, including ammonia emissions, space use, pen fouling, weight gain, carcass quality, perception of the stockkeeper, costs of the light system, and use of drinking water, electricity and medicines. Light treatments included a low (45 lux), medium (198 lux) and high (968 lux) uniform intensity, and a spatial gradient treatment ranging from 71 lux in the front to 330 lux in the back of each pen. The latter treatment aimed to improve the space use of functional areas. A total of 448 growing-finishing pigs were studied on a commercial farm using two consecutive batches of four rooms containing eight pens with seven pigs. Light intensity influenced some aspects of space use and pen fouling. For example, the proportion of pigs lying in the resting area was higher in the high and medium light intensity treatment than in the low intensity and gradient treatment. Moreover, the high-intensity treatment resulted in more fouling with faeces in the feeding area compared with the low-intensity and the gradient treatment. Ammonia emissions were higher in the gradient than in the low intensity treatment (not measured in medium and high intensity treatment). Furthermore, light intensity did not affect weight gain, carcass quality, water use and medicine use. The stockkeeper was content to work in all light conditions, but slightly preferred the medium intensity due to optimal visibility. Concerning economic performance, the costs of the light system and electricity use increased in the following order: low intensity, gradient, medium intensity, and high intensity. In conclusion, contrary to expectation the spatial gradient did not notably improve space use or reduce pen fouling, but rather increased ammonia emissions in comparison with uniform light. This is likely because the gradient could not be applied in an optimal way in the existing housing conditions. Among the other sustainability indicators, mainly electricity use and costs of the light system differed per treatment. These aspects can be improved by further optimising the number of light sources needed per pen to achieve the targeted intensities.

Abstract Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.

ABSTRACT: The effects of ambient temperature (AT) on total evaporative water loss from dairy cows at different relative humidity (RH) and air velocity (AV) levels were studied. Twenty Holstein dairy cows with an average parity of 2.0 ± 0.7 and body weight of 687 ± 46 kg participated in the study. Two climate-controlled respiration chambers were used. The experimental indoor climate was programmed to follow a diurnal pattern with AT at night being 9°C lower than during the day. Night AT was gradually increased from 7 to 21°C and day AT was increased from 16°C to 30°C within an 8-d period, both with an incremental change of 2°C/d. The effect of 3 RH levels with a diurnal pattern were studied as well, with low values during the day and high values during the night: low (day, 30%; night, 50%), medium (day, 45%; night, 70%), and high (day, 60%; night, 90%). The effects of AV were studied during the daytime at 3 levels: no fan (0.1 m/s), fan at medium speed (1.0 m/s), and fan at high speed (1.5 m/s). The medium and high AV levels were only combined with medium RH. In total, there were 5 treatments with 4 replicates each. The animals had free access to feed and water. Based on the water balance principle inside the respiration chambers, the total evaporative water loss from dairy cows at a daily level was quantified by measuring the mass of water in the incoming and outgoing air, condensed water, added water from a humidifier, and evaporative water from a wet floor, drinking bowl, manure reservoir, and water bucket. Water evaporation from a sample skin area was measured with a ventilated skin box, and water evaporation, through respiration with a face mask. The results show that RH/AV levels had no significant effect on total evaporative water loss, whereas the interaction effect between RH/AV with AT was significant. Cows at a high RH had a tendency for a lower increasing rate of evaporative water loss compared with cows at a low RH (0.61 vs. 0.79 kg/d per 1°C increase of AT). Cows at medium and high AV levels had a greater increasing rate than cows at low AV (0.91 and 0.95 vs. 0.71 kg/d per 1°C increase of AT, respectively). The increase of evaporative heat loss from dairy cows was mainly a result of the increase in evaporation (of sweat) from the skin. The skin water evaporation determined with the water balance method (less evaporation from respiration) and the ventilated skin box method showed no significant difference. The implication of this study is that cows at a high AT depend mainly on evaporative cooling from the skin. The ventilated skin box method, measuring only a small part of the skin during a short period during the day, can be a convenient and accurate way to determine the total cutaneous evaporative water loss from cows.

ABSTRACT: A linear relationship between heart rate (HR) and oxygen consumption (VO2) has been reported in homeothermic animals, indicating that is possible to estimate heat production through HR measurements. This relationship may depend on the animal activity and environmental conditions. The main objective of the present study was to evaluate the effect of the air temperature and animal posture and activity on heat production and VO2 in relation to HR. In addition, as a secondary objective, the energy cost of eating and ruminating versus idling and standing versus lying down was determined. Twelve Holstein lactating cows were housed inside climate-controlled respiration chambers for 8 d, where the air temperature was gradually increased from 7 to 21°C during the night and from 16 to 30°C during the day with daily increments of 2°C for both daytime and nighttime. During the 8-d data collection period, HR and gaseous exchange measurements were performed, and animal posture and activity were recorded continuously. The oxygen pulse (O2P), which represents the amount of oxygen that is consumed by the cow per heartbeat, was calculated as the ratio between VO2 and HR. Results showed that heat production and VO2 were linearly and positively associated with HR, but this relationship largely varied between individual cows. Within the range tested, O2P was unaffected by temperature, but we detected a tendency for an interaction of O2P with the temperature range tested during the night versus during the day. This indicates that the effect of air temperature on O2P is nonlinear. Standing and eating slightly increased O2P (1.0 and 2.5%) compared with lying down and idling, respectively, whereas rumination increased O2P by 5.1% compared with idling. It was concluded that the potential bias introduced by these effects on the O2P for the application of the technique is limited. The energy cost of eating and ruminating over idling was 223 ± 11 and 45 ± 6 kJ/kg0.75 per day, respectively, whereas the energy cost of standing over lying down was 53 ± 6 kJ/kg0.75 per day. We concluded that O2P in dairy cows was slightly affected by both animal posture and activity, but remained unaffected by air temperature within 8 to 32°C. Nonlinearity of the relationship between the O2P and air temperature suggests that caution is required extrapolating O2P beyond the temperature range evaluated in our experiment.

BackgroundThe COVID-19 pandemic caused a wave of acute respiratory distress syndrome (ARDS) with a high in-hospital mortality, especially in patients requiring invasive mechanical ventilation. Wharton Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) may counteract the pulmonary damage induced by the SARS-CoV-2 infection through pro-angiogenic effects, lung epithelial cell protection, and immunomodulation.MethodsIn this randomized, double-blind, placebo-controlled phase 2a trial, adult patients receiving invasive mechanical ventilation for SARS-CoV-2 induced moderate or severe ARDS were assigned to receive 1 intravenous infusion of 1 × 106 WJ-MSCs/kg or placebo within 48 h of invasive ventilation followed by 2 infusions of 0.5 × 106 WJ-MSCs/kg or placebo over 5 days. The primary endpoint was the percentage of patients with a PaO2/FiO2 > 200 on day 10.ResultsThirty patients were included from November 2020 to May 2021, 15 in the WJ-MSC group and 15 in the placebo group. We did not find any significant difference in the PaO2/FiO2 ratio at day 10, with 18 and 15% of WJ-MSCs and placebo-treated patients reaching a ratio >200, respectively. Survival did not differ in the 2 groups with a 20% mortality rate at day 90. While we observed a higher number of ventilation-free days at 28 days in the WJ-MSC arm, this difference was not statistically significant (median of 11 (0–22) vs. 0 (0–18), p = 0.2). The infusions were well tolerated, with a low incidence of anti-HLA alloimmunization after 90 days.ConclusionWhile treatment with WJ-MSCs appeared safe and feasible in patients with SARS-CoV2 moderate or severe ARDS in this phase 2a trial, the treatment was not associated with an increased percentage of patients with P/F > 200 at 10d, nor did 90 day mortality improve in the treated group.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT04625738, identifier NCT04625738.

This paper describes a model for the prediction of methane and ammonia emissions from fattening pig houses. This model was validated with continuous and discrete measurements using a reference method from two manure management systems (MMS): long storage (LS) in deep pits and short storage (SS) by daily flushing of a shallow pit with sloped walls and partial manure dilution. The average calculated methane and ammonia emissions corresponded well with the measured values. Based on the calculated and measured results, the average calculated CH4 emission (18.5 and 4.3 kg yr−1 per pig place) was in between the means from the continuous data from sensors (15.9 and 5.6 kg yr−1 per pig place) and the means from the discrete measurements using the reference method (22.0 and 3.1 kg yr−1 per pig place) for the LS and SS systems, respectively. The average calculated NH3 emission (2.6 and 1.4 kg yr−1 per pig place) corresponded well with the continuous data (2.6 and 1.2 kg yr−1 per pig place) and the discrete measurements using the reference method (2.7 and 1.0 kg yr−1 per pig place) from LS and SS, respectively. This model was able to predict the reduction potential for methane and ammonia emissions by the application of mitigation options. Furthermore, this model can be utilized as a predictive tool, enabling timely actions to be taken based on the emission prediction. The upgraded model with robust calculation rules, extensive validations, and a simplified interface can be a useful tool to assess the current situation and the impact of mitigation measures at the farm level.

Atomic layer deposition (ALD) is known for its unparalleled control over layer thickness and 3D conformality and could be the future technique of choice to tailor the pore size of ceramic nanofiltration membranes. However, a major challenge in tuning and functionalizing a multichannel ceramic membrane is posed by its large internal pore volume, which needs to be evacuated during ALD cycling. This may require significant energy and processing time. This study presents a new reactor design, operating at atmospheric pressure, that is able to deposit thin layers in the pores of ceramic membranes. In this design, the reactor wall is formed by the industrial tubular ceramic membrane itself, and carrier gas flows are employed to transport the precursor and co-reactant vapors to the reactive surface groups present on the membrane surface. The layer growth for atmospheric-pressure ALD in this case proceeds similarly to that for state-of-the-art vacuum-based ALD. Moreover, for membrane preparation, this new reactor design has three advantages: (i) monolayers are deposited only at the outer pore mouths rather than in the entire bulk of the porous membrane substrate, resulting in reduced flow resistances for liquid permeation; (ii) an in-line gas permeation method was developed to follow the layer growth in the pores during the deposition process, allowing more precise control over the finished membrane; and (iii) expensive vacuum components and cleanroom environment are eliminated. This opens up a new avenue for ceramic membrane development with nano-scale precision using ALD at atmospheric pressure.

ABSTRACT: The focus of this study was to identify the effects of increasing ambient temperature (T) at different relative humidity (RH) and air velocity (AV) levels on heat loss from the skin surface and through respiration of dairy cows. Twenty Holstein dairy cows with an average parity of 2.0 ± 0.7 and body weight of 687 ± 46 kg participated in the study. Two climate-controlled respiration chambers were used. The experimental indoor climate was programmed to follow a diurnal pattern with ambient T at night being 9°C lower than during the day. Night ambient T was gradually increased from 7 to 21°C and day ambient T was increased from 16 to 30°C within an 8-d period, both with an incremental change of 2°C per day. A diurnal pattern for RH was created as well, with low values during the day and high values during the night (low: RH_l = 30–50%; medium: RH_m = 45–70%; and high: RH_h = 60–90%). The effects of AV were studied during daytime at 3 levels (no fan: AV_l = 0.1 m/s; fan at medium speed: AV_m = 1.0 m/s; and fan at high speed: AV_h = 1.5 m/s). The AV_m and AV_h were combined only with RH_m. In total, there were 5 treatments with 4 replicates (cows) for each. Effects of short and long exposure time to warm condition were evaluated by collecting data 2 times a day, in the morning (short: 1-h exposure time) and afternoon (long: 8-h exposure time). The cows were allowed to adapt to the experimental conditions during 3 d before the main 8-d experimental period. The cows had free access to feed and water. Sensible heat loss (SHL) and latent heat loss (LHL) from the skin surface were measured using a ventilated skin box placed on the belly of the cow. These heat losses from respiration were measured with a face mask covering the cow's nose and mouth. The results showed that skin SHL decreased with increasing ambient T and the decreasing rate was not affected by RH or AV. The average skin SHL, however, was higher under medium and high AV levels, whereas it was similar under different RH levels. The skin LHL increased with increasing ambient T. There was no effect of RH on the increasing rate of LHL with ambient T. A larger increasing rate of skin LHL with ambient T was observed at high AV level compared with the other levels. Both RH and AV had no significant effects on respiration SHL or LHL. The cows lost more skin sensible heat and total respiration heat under long exposure than short exposure. When ambient T was below 20°C the total LHL (skin + respiration) represented approx. 50% of total heat loss, whereas above 28°C the LHL accounted for more than 70% of the total heat loss. Respiration heat loss increased by 34 and 24% under short and long exposures when ambient T rose from 16 to 32°C.

ABSTRACT: This study determined the effects of increasing ambient temperature (T) at different relative humidity (RH) and air velocity (AV) levels on the physiological and productive responses of dairy cows. Twenty Holstein dairy cows were housed inside climate-controlled respiration chambers, in which the climate was programmed to follow a daily pattern of lower night and higher day T with a 9°C difference, excluding effects from sun radiation. Within our 8-d data collection period, T was gradually increased from 7 to 21°C during the night (12 h) and 16 to 30°C during the day (12 h), with an incremental change of 2°C per day for both nighttime and daytime T. During each research period, RH and AV were kept constant at 1 of 5 treatment levels. A diurnal pattern for RH was created, with lower levels during the day and higher levels during the night: low (RH_l: 30–50%), medium (RH_m: 45–70%), and high (RH_h: 60–90%). The effects of AV were studied during the day at 3 levels: no fan (AV_l: 0.1 m/s), fan at medium speed (AV_m: 1.0 m/s), and fan at high speed (AV_h: 1.5 m/s). Effects of short and long exposure time to increasing T were evaluated by collecting data 2 times a day: in the morning [short: 1 h (or less) − exposure time] and afternoon (long: 8 h − exposure time). The animals had free access to feed and water and both were ad libitum. Respiration rate (RR), rectal temperature (RT), skin temperature (ST), dry matter intake, water intake, milk yield, and composition were measured. The inflection point temperatures (IPt) at which a certain variable started to change were determined for the different RH and AV levels and different exposure times. Results showed that IPt under long exposure time for RR (first indicator) varied between 18.9 and 25.5°C but was between 20.1 and 25.9°C for RT (a delayed indicator). The IPt for both RR and RT decreased with higher RH levels, whereas IPt increased with higher AV for RR but gave a minor change for RT. The ST was positively correlated with ambient T and ST was not affected by RH but significantly affected by AV. For RR, all IPt was lower under long exposure time than under short exposure time. The combination of higher RH levels and low AV level negatively affected dry matter intake. Water intake increased under all treatments except RH_l-AV_l. Treatment RH_h-AV_l negatively affected milk protein and fat yield, whereas treatments RH_m-AV_m and RH_m-AV_h reduced milk fat yield. We concluded that RH and AV significantly affected the responses of RR, RT, ST, and productive performance of high-producing Holstein cows. These responses already occurred at moderate ambient T of 19 to 26°C.

The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and application for clinicians. We assessed 27 predictive models, broadly divided into six categories of alloreactivity prediction: ligand-ligand, receptor-ligand, educational, KIR haplotype-based, KIR matching and KIR allelic polymorphism. The models were applied to 78 NGS-typed donor/recipient pairs undergoing allogeneic HSCT in genoidentical (n=43) or haploidentical (n=35) matchings. Correlations between different predictive models differed widely, suggesting that the choice of the model in predicting NK alloreactivity matters. For example, two broadly used models, educational and receptor-ligand, led to opposing predictions especially in the genoidentical cohort. Correlations also depended on the matching fashion, suggesting that this parameter should also be taken into account in the choice of the scoring strategy. The number of centromeric B-motifs was the only model strongly correlated with the incidence of acute graft-versus-host disease in our set of patients in both the genoidentical and the haploidentical cohorts, suggesting that KIR-based alloreactivity, not MHC mismatches, are responsible for it. To our best knowledge, this paper is the first to experimentally compare NK alloreactivity prediction models within a cohort of genoidentical and haploidentical donor-recipient pairs. This study helps to resolve current discrepancies in KIR-based alloreactivity predictions and highlights the need for deeper consideration of the models used in clinical studies as well as in medical practice.

This work brings novel insights into the existing knowledge on the deposition of films containing boron (B), carbon (C), nitrogen (N), and aluminum (Al). The (Al)BCN films are obtained at low substrate temperatures (TS) of 250–400 °C from triethylborane, ammonia (NH3), and trimethylaluminum. For BCN films, a nearly similar elemental composition of B0.42C0.41N0.15O0.02, with 1–2 at. % variations, is observed for substantial ranges of TS and NH3-exposure time. This can indicate a similar growth mechanism and/or formation of a single-phase material. While excluding precursor underdosing, a remarkable dependence of growth rate per cycle (GPC) on total gas pressure (Ptot) is observed. The GPC approaches near saturation regime for Ptot between 1 and 10 mbar, for TS = 330–375 °C, which might support the occurrence of a surface-adduct assisted pathway. The level of GPC saturation is influenced by TS. For a wide range of process conditions, N-share in the films slightly varies between 12 and 16 at. %. C-share only changes between 40 and 42 at. %. The attempt to increase N-share by dissociating NH3 into NH2 radicals by hot wire assistance remarkably shows the opposite effect, i.e., a decrease in the N-share from 15 to 6 at. %. This is accompanied by a corresponding increase in the B- and, in particular, C-shares, suggesting that the removal of carbon can occur via the incorporation of nitrogen. For AlBCN films, changing Ptot has a strong effect on their elemental composition. At Ptot = 10 mbar, Al-deficient films grow, whereas a Ptot of 0.2 mbar leads to mainly AlN-containing films with some inclusions of BN.

Aims Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study, we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. Methods and results The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were pre-specified, and death was categorized as cardiovascular, non-cardiovascular, or unknown origin. Mortality rates were calculated from Kaplan–Meier estimates. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Two-year mortality rate was 16.4% [confidence interval (CI): 14.0–18.7%], with 50% of patients dying from a non-cardiovascular cause. Multivariate baseline predictors of 2-year mortality included age [hazard ratio (HR) 1.05, CI: 1.03–1.08, per year increase], heart failure (HR 1.73, CI: 1.24–2.41), vascular disease (HR 1.47, CI: 1.05–2.05), valvular disease (HR 1.63, CI: 1.15–2.33), abnormal liver function (HR 1.80, CI: 1.02–3.17), and abnormal renal function (HR 1.58, CI: 1.10–2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. Conclusion One in six patients died within 2 years after LAAO. We identified six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO. Clinical trial registration The original EWOLUTION registry was registered at clinicaltrials.gov under identifier NCT01972282. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the recruitment of viable alternative donors, particularly haploidentical donors. Over 95% of patients have at least two potential haploidentical donors available to them. To identify the best haploidentical donor, the assessment of new immunogenetic criteria could help. To this end, the clinical benefit of KIR genotyping in aHSCT has been widely studied but remains contentious. This review aims to evaluate the importance of KIR-driven NK cell alloreactivity in the context of aHSCT and explain potential reasons for the discrepancies in the literature. Here, through a non-systematic review, we highlight how the studies in this field and their respective predictive models or scoring strategies could be conceptually opposed, explaining why the role of NK cells remains unclear in aHCST outcomes. We evaluate the limitations of each published prediction model and describe how every scoring strategy to date only partly delivers the requirements for optimally effective NK cells in aHSCT. Finally, we propose approaches toward finding the optimal use of KIR genotyping in aHSCT for a unified criterion for donor selection.